title: Alpha interferon restricts human T-lymphotropic virus type 1 and 2 de novo infection through PKR activation.
abstract: Type I interferon (IFN-I) inhibits the replication of different viruses. However, the effect of IFN-I on the human T-lymphotropic virus type 1 (HTLV-1) viral cycle is controversial. Here, we investigated the consequences of IFN-α addition for different steps of HTLV-1 and HTLV-2 infection. We first show that alpha interferon (IFN-α) efficiently impairs HTLV-1 and HTLV-2 de novo infection in a T cell line and in primary lymphocytes. Using pseudotyped viruses expressing HTLV-1 envelope, we then show that cell-free infection is insensitive to IFN-α, demonstrating that the cytokine does not affect the early stages of the viral cycle. In contrast, intracellular levels of Gag, Env, or Tax protein are affected by IFN-α treatment in T cells, primary lymphocytes, or 293T cells transfected with HTLV-1 or HTLV-2 molecular clones, demonstrating that IFN-α acts during the late stages of infection. We show that IFN-α does not affect Tax-mediated transcription and acts at a posttranscriptional level. Using either small interfering RNA (siRNA) directed against PKR or a PKR inhibitor, we demonstrate that PKR, whose expression is induced by interferon, plays a major role in IFN-α-induced HTLV-1/2 inhibition. These results indicate that IFN-α has a strong repressive effect on the HTLV-1 and HTLV-2 viral cycle during de novo infection of cells that are natural targets of the viruses.
authors.affiliation: Equipe Oncogenèse Rétrovirale.
authors.forename: Anne
authors.initials: A
authors.lastname: Cachat
authors.forename: Sébastien Alain
authors.initials: SA
authors.lastname: Chevalier
authors.forename: Sandrine
authors.initials: S
authors.lastname: Alais
authors.forename: Nga Ling
authors.initials: NL
authors.lastname: Ko
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
authors.forename: Chloé
authors.initials: C
authors.lastname: Journo
authors.forename: Hélène
authors.initials: H
authors.lastname: Dutartre
authors.forename: Renaud
authors.initials: R
authors.lastname: Mahieux
mesh_terms: D002460:Cell Line; D004789:Enzyme Activation; D015490:HTLV-I Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D015491:HTLV-II Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D015367:Human T-lymphotropic virus 2 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C583541:EIF2AK1 protein, human; D019892:eIF-2 Kinase